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EPIGENETIC MODULATION OF MYOCARDIAL ANGIOGENIC BALANCE: AN EMERGING THERAPEUTIC PERSPECTIVE FOR ADULT FAILING HEART
No full textThe term "Epigenetics" refers to chromatin-based pathways involved in the regulation of gene expression without altering DNA sequence. Suppression of angiogenesis may be related to cardiac dysfunction following alterations in capillary microvasculature. An understanding of the relationship between angiogenesis and cardiac remodeling remains the major limitation in order to address the weak self-renewal ability of the adult failing heart. In physiological conditions, genes responsible for sustaining the angiogenic ability of the mature endothelial cells can be categorized into pro- and anti-angiogenic genes. The balanced expression of angiogenic genes maintains a state of equilibrium in capillary density of the adult myocardium. In the context of post-ischemic myocardial dysfunction, transcriptional and posttranscriptional modifications of the gene pool are involved in alterations of angiogenic balance in capillary microvasculature, angiogenesis, myocardial perfusion/contractility match and contractile function. The regulation of angiogenic gene expression by different epigenetic modifications may induce the formation of new vessels from coronary mature endothelial cells rather than endothelial progenitor cells. The role of proangiogenic epigenetic activators is emerging as a new actor in the modulation of the angiogenic balance of failing heart. In fact, the development of an ideal method to promote myocardial revascularization, while attenuating cardiac remodeling, is still a challenging issue. The present review will examine emerging studies on the epigenetic mechanisms involved in the regulation of function and angiogenic ability of mature endothelial cells residing in the adult myocardium
Long term intake of barley beta-D-glucan attenuates glucose intolerance, mood disorders and cognitive decline in high-fat diet-induced obese mice exposed to chronic psychosocial stress
No full textHigh-fat diet (HFD)-induced obesity causes insulin resistance and increases vulnerability to chronic psychosocial stress-induced dysfunctions, including anxiety and mood disorders, cognitive decline and myocardial ischemia. The inhibition of class I histone deacetylases leads to metabolic homeostasis and dietary barley (1.3) beta-D-glucan (β-D-glucan), a water-soluble polysaccharide, increases levels of histone H4 acetylation. We tested whether the long-term intake of β-D-glucan prevents glucose intolerance, affective disorders and cognitive decline in stressed obese mice. 24 male mice C57BL/6 were fed three different diets for 18 wks: 1) standard diet (SD; 10% Kcal from fat; n=8), 2) HFD (58% Kcal from fat; n=8) or 3) HFD supplemented with 3% w/v β-D-glucan (HFD+BG; 58% Kcal from fat; n=8). From the 16th to the 18th wk all animals underwent to the resident-intruder stress test. Before and after chronic stress, the anxiety-related behaviour and the spatial working memory were evaluated by elevated plus-maze (PM; entries in open arms, %) and Y-maze test (YM; spontaneous alternation, %). At the end of the experiment, plasma brain derived neurotrophic factor (BDNF) and the hippocampal expression of tropomyosin-related kinase B (TrKB, the BDNF receptor) were evaluated because of their key role in energy balance and in the pathogenesis of affective and cognitive disorders. At the 16th wk, HFD’s body weight was increased compared to SD group (+36.6%, p<0.01), but the β-D-glucan supplementation prevented the HFD-induced weight gain. The glucose tolerance test area under the curve (AUC; 0–120 min) was higher in HFD than SD mice fasted (447.7 ± 55 vs 259.1 ± 23.4 mg/dL*min: p<0.001); although, it was lower (−25.8%, p<0.01) in the HFD+BG compared to HFD group. Compared to SD group, open arm activity at the16th week was lower in the HFD (−250%, p<0.001) than in the HFD+BG group (−55.5% p<0.05). After stress, the entries in open arms were absent in HFD mice and were further reduced (−75%, p<0.01) in SD animals, yet the open arm activity was unchanged in HFD+BG group. Spatial working memory after 16 wks. was similar in all groups, but after stress it was reduced only in HFD mice (−18.9%, p<0.01). Compared to SD, reduction of BDNF plasma levels was detected in HFD mice, but not in HFD+BG group (SD, 66 ± 22 pg/ml; HFD, 27 ± 11 pg/ml; HFD+BG, 78 ± 32 pg/ml, p<0.05). The hippocampal expression of TrKB in HFD+BG group was significantly higher than HFD mice (HFD+BG, 0.63 ± 0.13 a.u.; SD, 0.5± 0.1 a.u.; HFD, 0.44 ± 0.05 a.u., p<0.05). In conclusion, β-D-glucan intake attenuates glucose intolerance and improves the stress-induced response in obese mice through the upregulation of hippocampal BDNF/TrkB pathway. Our data provide a basis for developing a new nutraceutical approach for the protection against obesity/stress-related disorders
Downregulation of von Willebrand Factor prevents Ang II-induced endothelin-1 expression independently of eNOS activation in porcine endothelial cells
No full textPurpose: Angiotensin II (AngII) generated under conditions of myocardial ischemia and reperfusion increases endothelial levels of endothelin (ET)-1, von Willebrand factor (vWF) and anion superoxide (O2-), which lead to progressive coronary endothelial dysfunction. Recent study described that vWF blockade improves endothelial function in coronary patients, but the mechanisms are still unknown.
Our study investigated whether the downregulation of vWF modulates the ET-1 level, eNOS activity and O2- generation in porcine aortic endothelial cells (PAOECs) chronically exposed to AngII.
Methods: The silencing of vWF in PAOECs was induced with selective short interference RNA. Protein expression of endothelial vWF, ET-1, eNOS and phospho-Ser1177eNOS (p-eNOS) was measured by western blotting in wild type and vWFknockdown cells exposed to vehicle or AngII (100nM for 24h). O2- formation was measured by dihydroethidium staining. In additional experiments, wild type and
vWF-knockdown cells were treated with phorbol 12-myristate 13-acetate (PMA, 5nM for 48h), a nonsubtype selective agonist of protein kinase type C and inhibitor of eNOS activity.
Results: Nearly 65% silencing of vWF cell viability and growth were not impaired. Levels of ET-1, phospho-Ser1177eNOS (peNOS)/eNOS ratio and O2- were unchanged in vWF-knockdown compared to wild type cells under normal conditions.
Conversely, ET-1expression was reduced by 93.7±4% (P<0.0001) in the presence of normal p-eNOS/eNOS ratio in vWF-knockdown cells under oxidative microenvironment; although, the intracellular load of O2- was reduced by 33.3±2% in vWF-knockdown cells with lower level of Mn superoxide dismutase. In additional experiments, the inhibition of eNOS activity by PMA did not reverse the downregulation of ET-1.
Conclusions: We demonstrated that vWF-knockdown modulates the response of PAOECs to chronic exposure to AngII by preventing cell death, reducing ET-1 and O2- production without affecting endothelial function. Our findings support the usefulness of vWF as upstream modulator of ET-1 expression under oxidative stress
Comparison of canine plasma and serum as a source of mitochondria-rich microvesicles boosting cardiomyocyte proliferation
No full textLong-term dietary intake of pasta enriched with barley (1–3) beta-d-glucan induces neovascularization-mediated cardioprotection against ischemia/reperfusion injury in mice
No full textBackground: The modulation of angiogenesis is known to be a strategy to increase heart
resistance to ischemia/reperfusion (I/R). Whereas the angiogenic activity of barley (1-
3)beta-D-Glucan (BG) have been characterized in vitro, there are no clear experimental
data demonstrating that chronic dietary intake and intestinal absorption of BG actually
protects the heart against I/R. We tested whether long-term consumption of 3% w/v BG
included in normal pasta would increase myocardial angiogenesis and render the heart
of mice more resistant to I/R.
Materials and methods: Healthy adult male C57BL/6 mice were fed for 5 weeks with a
low-fat diet supplemented with pasta enriched with BG (3g/100mg) (BG, n=15) or
regular pasta (control, n=15). Food intake, glucose tolerance test and cardiac function
were weekly assessed. At fifth week of diet, anesthetized mice underwent to 30 min of
cardiac ischemia followed by 60 min of reperfusion. The myocardial infarction
was induced by ligation of the left anterior descending artery. The myocardial capillary
density and infarct size/area at risk were assessed ex vivo. Myocardial Vascular
Endothelial Growth Factor 165 (VEGF165) expression and anion superoxide (O2-) levels
were measured respectively by western blot and dihydroethidium staining. To evaluate the
paracrine activation of protective angiogenesis by BG, we measured the expression of
VEGF165, a well known pro-angiogenic growth factor, in endothelial cells exposed for 7
days to 3% BG. Finally, we examined the expression of dectin-1, a receptor of BG, in both
endothelial cells and cardiomyocytes.
Results: At similar food intake, 3% w/v BG did not affect body weight, glucose metabolism
and cardiac function of mice. At the end of reperfusion, BG mice survived 50±2% more
than control (P<0.01). Infarct size/area at risk and myocardial O2- load were reduced
respectively by 62±5% (P<0.001) and 35±4% (P<0.0001) in β-D-glucan mice. Myocardial
capillary density and VEGF165 expression were increased respectively by 12±0.6%
(P<0.05) and 47.6±1% (P<0.001) in BG group compared to control mice. In vitro,
VEGF165 expression was significantly increased in BG-treated endothelial cells
(P<0.001). Dectin-1 was expressed in endothelial cells, but not in cardiomyocytes.
Conclusions: Long-term intake of BG-rich diet augments myocardial capillary density and
reduces infarct size by sustained expression of VEGF165 in endothelial cells, which
express dectin-1. Our findings suggest important potential health benefits of pasta-rich in
BG and emphasize the need to develop BG-rich functional foods with protective activities
for increasing heart resistance to I/R injury
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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